The long term goal of Project IV is to define the genetic and biological bases for abnormalities seen in Down Syndrome (Trisomy 21, Ts21) patients, using genetically defined and genetically manipulated mouse model systems. The Down Syndrome region of human Chromosome (Chr) 21 is conserved in at least three mouse chromosomes -- Chrs 10, 16, and 17. In my laboratory, we have produced a mouse stain that carries segmental trisomy for most of the region of mouse Chromosome (Chr) 16 that is homologous with Down Syndrome region of human Chr 21. In Dr. Gearhart;s laboratory, transgenic strains carrying extra copies of genes from the Chr 10 and Chr 17 segments are being produced. The objectives of Project IV are to (1) combined the Chr 16 trisomic segment with these transgenes by standard breeding protocols, (2) study the pathologic effects of the combinations produced, and (3) provide an intact adult mouse model for testing therapies.